The relationship of plasma levels of pindolol in hypertensive patients to effects on blood pressure, plasma renin and plasma noradrenaline levels. 1. Fifteen, previously untreated, hypertensive patients were given 20 mg of pindolol, orally. The systolic and diastolic blood pressures fell significantly in 1 h; the effect was maximal 4 h after pindolol, and persisted for at least 8 h. 2. After oral administration of 20 mg of pindolol, its concentration in the plasma reached a peak in 2-3 h. At the end of 8 h, pindolol was not detectable in the plasma. 3. There was a significant relationship between the peak concentration of pindolol in plasma and the maximal change in blood pressure in fifteen previously untreated hypertensive patients. In a separate study of nine-nine hypertensive outpatients taking 15-80 mg of pindolol daily, the blood pressure responses corresponded generally to the concentration of pindolol in plasma 2-3 h after the morning dose. 4. There were no significant changes in plasma renin activity, plasma renin concentration or plasma noradrenaline concentration in the previously untreated patients taking 20 mg of pindolol. There was no relationship between initial plasma renin or noradrenaline levels and blood pressure responses to pindolol. Nor was there any significant relationship between the changes in plasma renin or noradrenaline levels and the changes in blood pressure.


Human cardiorespiratory responses to acute cold exposure. 1. Respiratory and circulatory functions of minimally clad human subjects were studied before and during acute exposure to ambient temperatures of 4.5-6.5 degrees C. 2. After 1 h of cold exposure, subjects showed increases of ventilation, O2 UPTAKE AND CARDIAC OUTPUT. Rectal temperatures fell. 3. During exercise in the cold conditions, oxygen uptake and cardiac output were greater than during the same exercise at normal temperature. 4. The increased cardiac output during cold exposure was achieved by an increase of stroke volume rather than heart rate; this finding is in contrast to changes during bicycle exercise and isometric exercise at normal ambient temperatures. 5. We conclude that the cardiorespiratory effects of cold exposure are not superseded by the response to moderate exercise. The difference between heart rate and stroke volume at increased levels of cardiac output during exercise at normal temperatures and during rest and exercise in cold conditions may be explained by changes of arterial baroreceptor input and of blood catecholamine levels.


Measurement of glomerular filtration rate by fluorescent excitation of non-radioactive meglumine iothalamate. The clearance of non-radioactive meglumine Iothalamate (Conray 60), assayed by fluorescent excitation analysis, has been shown to be a good indicator of the glomerular filtration rate (GFR). Investigations in rats by the constant infusion technique showed a good correlation with insulin clearance. In a group of ten children and one adult, we obtained excellent agreement between GFR determinations by clearance of Conray 60 and I-125 sodium Iothalamate, using the single injection technique, and taking samples from 10 min to 4 hr after injection. The decay curve was resolved into two exponential components. We have also shown that the 3 and 4 hr samples, fitted to a single exponential function, yield good agreement with GFR determinations using a double exponential model. The GFR determination method presented here is accurate, simple, cost effective, and involves no radiation exposure to the patient.


Effects of blockade of extraneuronal uptake on responses to isoprenaline in perfused rat heart. 1. Isolated rat hearts accumulated 102 pmol/g wet wt/min of isoprenaline when perfused for 5 min with 0-6 muM (+/-)-3H-isoprenaline. 2. The 3-methoxy derivative of isoprenaline ('methoxy isoprenaline') (10 muM) significantly inhibited this uptake by 57%, metanephrine (10 muM) by 29% and normetanephrine (10 muM) by 21%. 3. (+/-)-Isoprenaline (0-6 muM) infused into isolated perfused rat hearts for 5 min activated glycogen phosphorylase 2-4-fold. Normetanephrine (10 muM) or metanephrine (10 muM included in the perfusate significantly potentiated this activation, but 3-0-methyl isoprenaline (10 muM significantly reduced it. However, 3-0-methyl isoprenaline potentiated the ability of 4-8 muM isoprenaline to stimulate phosphorylase. 4. Neither metanephrine (10 muM) nor normetanephrine (10 muM) altered peak inotropic responses to injections of (+/-)-isoprenaline into the solution perfusing isolated rat hearts. 3-0-methyl isoprenaline (10 muM) shifted the isoprenaline dose-response curve to the right, but did not affect the inotropic responses to CaCl2, confirming that 3-0-methyl isoprenaline possess beta-adrenoceptor antagonist activity. 5. Inotropic responses to isoprenaline were significantly prolonged by both 3-0-methyl isoprenaline and normetanephrine (10 muM). 6. These results indicate that blockade of extraneuronal accumulation of catecholamines causes potentiation of both metabolic and mechanical beta-adrenoceptor-mediated responses of the heart to isoprenaline. It is suggested that Uptake2 and the cardiac beta-adrenoceptor are separate entities, and that the beta-adrenoceptor is localized in the sarcolemma. The physiological function of Uptake2 may be to help clear the sympathetic synaptic gap of liberated neurotransmitter.


Effects of brain lesions on the antinociceptive properties of morphine in rats. 1. Electrolytic lesions were made in various brain regions of the rat, and the effects of these lesions on nociceptive threshold and the antinociceptive actions of morphine were tested using a shock titration technique. 2. Lesions in the medial thalamus, the periaqueductal grey area, or the caudate nucleus, had no effect on the nociceptive threshold; whereas, lesions in the posterior hypothalamus resulted in a small but statistically significant increase in this threshold. 3. Morphine administered intraperitoneally to rats having histologically verified lesions in the posterior hypothalamus, the caudate nucleus or the periaqueductal grey area resulted in a 15-30% increase in the nociceptive threshold. This increase was similar to that observed in unoperated control rats. On the other hand, injections of morphine into animals having greater than 50% of the medial thalamus destroyed produced a highly significant increase of 95% in the threshold. This potentiation of the antinociceptive action of morphine was not observed in rats having less than 50% destruction of the medial thalamus.


Clearances of complement components, C3 proactivator and other serum proteins in chronic membranoproliferative glomerulonephritis (CMPGN). In chronic membranoproliferative glomerulonephritis (CMPGN) the activation of the complement system through the properdin pathway plays an important role. The clearance of complement components and of the C3-proactivator (C3-PA) have been determined in 18 patients. Hemolytically active C5, C6, C7 and C3-PA were detected in the urine for the first time. The clearances of the complement components  did not correlate with the clearances of other serum proteins with similar molecular weights. The specificities of the single complement components in the urine were tested by specific complement inhibitors such as hydrazine, KSCN, and the C4-inactivating factor.


Plasma renin concentration in hypertension produced by unilateral renal artery constriction in the rat. 1. Plasma renin concentration (PRC) and blood pressure were studied sequentially, 24 h to 42 days post-operatively, in rats subjected to unilateral renal artery constriction without contralateral nephrectomy. 2. The PRC of rats failing to develop hypertension remained normal, whereas the mean PRC of twenty-two rats that became hypertensive was five times normal on day 14 of the study when the hypertension was becoming established. 3. In eleven of the twenty-two rats that became hypertensive, PRC did not exceed the upper limit of normal. In the remaining hypertensive rats, the increase in PRC was not always temporally related to the increase in blood pressure. A significant correlation between PRC and blood pressure did not emerge until day 35 of the study. 4. Despite these anomalies, linear regression analysis of 169 pairs of PRC and blood pressure measurements during the 42 day period of development of hypertension in twenty-two rats revealed a highly significant correlation between log PRC and blood pressure (P smaller than 0.001). 5. It is concluded that factors other than the plasma concentration of renin are involved in the early stages of development of hypertension induced by renal artery constriction. Nevertheless, PRC and blood pressure are intricately related.


Abolition of the renin-releasing action of frusemide by acute renal denervation in dogs. 1. The effects of infusions of frusemide at low (0.05-0.1 mg.kg-1.min-1) and high (0.5-2.0 mg.kg-1.min-1) rates were studied on renin secretion and urinary outputs of sodium and potassium in anaesthetized dogs in which one kidney was removed and the remaining kidney was either innervated or denervated. 2. When the kidney was innervated, low rates of infusion of frusemide did not significantly affect renin secretion if urinary volume and sodium losses were replaced. Without replacement of urinary losses, renin secretion increased at sodium deficits of 0.7-0.9 mmol.kg-1 in the presence of elevated rates of sodium and potassium excretion. 3. High rates of infusion of frusemide caused an immediate increase in renin secretion from innervated kidneys which was not related to urinary losses. 4. Denervation of the kidney increased the urinary outputs of sodium and potassium while it decreased the rate of renin secretion to one-tenth of the resting value. 5. Denervation of the kidney abolished the renin-releasing action of frusemide at both low and high infusion rates even when the sodium deficit amounted to 4.3 mmol.kg-1. 6. Constriction of the aorta producing a fall of 10-30 mmHg in perfusion pressure raised the rate of renin secretion from denervated kidneys to control levels and partially restored the renin-releasing action of frusemide at high infusion rates. 7. The findings indicate that frusemide has a site of action apart from the macula densa in mediating renin release.


Nephronophthisis and tapetoretinal degeneration associated with liver fibrosis. A 12 year-old boy was referred because of general weakness, enuresis and pallor which had been present for at least six months. Previously, the child had been hospitalized at the age of five, because of mental retardation and hepatosplenomegaly, for which no cause could be found. He had severe renal insufficiency, with all the hallmarks of nephronophthisis. In addition his vision was very poor and fundoscopy revealed tapetoretinal degeneration. The liver and spleen were grossly enlarged. Liver function was almost completely normal, but histology showed diffuse periportal febrosis with profiferation of the bile ducts. This observation seems to confirm the existence of a new syndrome, associating nephronophthisis and liver fibrosis as described by Boichis and coworkers (1973).


Urea index and nitrogen balance in uremic patients on miminal nitrogen intakes. Normal anduremic subjects were studied on different protein intakes. The uremic patients were also given minimal amounts of nitrogen in the form of 8 essential amino acids, with or without the addition of histidine. It was noticed that as little as 416 mg of essential amino acid nitrogen was sufficient to cover body needs if enough non-essential nitrogen was present. It was also demonstrated that on low-nitrogen intakes, the ratio of urinary urea to total urinary nitrogen varied with nitrogen balance.


Salt loss as a possible mechanism eliciting an acute malignant phase in renal hypertensive rats. 1. The acute malignant phase of hypertension in rats with an untouched contralateral kidney is characterized by salt and fluid loss, increased fluid intake, decrease in body-weight gain, and reduced food consumption. Plasma concentrations of sodium and potassium were reduced, and plasma angiotensin II rose to about four times normal. 2. To investigate the significance of an untouched contralateral kidney for the development of the acute malignant phase in renal hypertensive rats, comparative studies were undertaken in unilaterally nephrectomized rats with stenosis of the remaining renal artery and in rats with bilateral renal artery stenosis. In addition, the effect of declamping one renal artery in rats with bilateral stenosis was studied. 3. In unilaterally nephrectomized rats, no signs of sodium and fluid loss were demonstrable, despite marked increase in blood pressure. Similarly, rats with bilateral renal artery stenosis had no acute malignant phase of hypertension. 4. In hypertensive rats with bilateral stenosis, removal of the clip from one renal artery was followed by an immediate fall in blood pressure and a subsequent gradual increase. Eleven of sixteen rats lost salt and fluid and developed an acute malignant phase. Plasma angiotensin II was high and serum urea elevated. 5. Consumption of 2% saline in addition to water as drinking fluid had a beneficial effect, since only five of fourteen rats showed signs of the acute malignant phase, which were milder than in rats on water only. 6. It is concluded that the untouched contralateral kidney is responsible for the negative salt and water balance and its consequences, which are characteristic of the acute malignant phase of experimental renal hypertension.


Effects of changes in external calcium concentration and frequency of stimulation on inotropic responses to isoprenaline and tolbutamide in rabbit atria. 1. Driven left atrial preparations were used to study inotropic responses to isoprenaline and tolbutamide. 2. Decreasing the external calcium concentration from 2.2 to 1.1 and 0.55 mM decreased resting force of contraction but increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 3. Decreasing the external calcium concentration from 2.2 to 1.1 mM also increased the maximal inotropic responses to tolbutamide. These responses were 23- and 44-fold less than those to isoprenaline at equivalent calcium concentrations. 4. Preparations maintained in 1.1 mM calcium were used to compare inotropic responses to isoprenaline and tolbutamide at different frequencies of stimulation. 5. Decreasing the frequency of stimulation from 4 to 2 or 1 Hz decreased the resting force of contraction and increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 6. No significant inotropic responses to tolbutamide were observed at 4 Hz. Positive inotropic responses of similar magnitude occurred at 2 and 1 Hz. The maximal inotropic responses at these frequencies were 43- and 127-fold less than those to isoprenaline. 7. It is concluded that tolbutamide is a very weak inotropic agent.


Cardiovascular effects of prazosin in normotensive and genetically hypertensive rats. 1. The cardiovascular effects of prazosin, a new antihypertensive drug, were studied in normotensive and genetically hypertensive rats. 2. Prazosin, infused intra-arterially, lowered vascular resistance in the blood-perfused rat hind limb. This effect was dependent on the presence of intact sympathetic innervation to the limb; no direct vasodilatation was demonstrated. In this preparation prazosin infusion reduced vasoconstrictor responses to noradrenaline. 3. In the saline-perfused rat mesenteric artery preparation prazosin reduced responses to noradrenaline and sympathetic nerve stimulation but not those to serotonin and vasopressin. Prazosin was more potent than phentolamine, on a molar basis, in reducing the vasoconstrictor effects of noradrenaline. 4. A comparison of the effects of prazosin injected intravenously and into a lateral cerebral ventricle failed to show any central action of the drug on blood pressure. Experiments using the donor blood-perfused, vascularly isolated rat hind limb preparation confirmed that the sympatholytic effect of prazosin occurred within the limb itself.


The incorporation of ammonia nitrogen into albumin in man: the effects of diet, uremia and growth hormone. 15 N-ammonium chloride was given orally to 17 individuals in 20 studies. Retention of 15N by those with normal renal function was inversely proportional to the protein intake; enrichment of albumin with 15N increased during protein restriction. Protein restriction appeared to be a more potent stimulus to the synthetic use of ammonia than a large pool of urea nitrogen. Both retention of isotope and enrichment of albumin decreased when a high protein diet was given. Enrichment of albumin with 15N in response to 10 or 20 mg of growth hormone daily was similar to that in healthy individuals on a 20 g protein diet for 3 weeks. The relevance of these findings to the nutritional potential of recycled urea nitrogen is discussed.


Clearance from the circulation of the rat and whole-body autoradiography in the mouse of 125I-labelled neurophysins. 1. The rate of clearance of 125I-labelled porcine neurophysins I and II from the circulation of the rat has an initial fast component followed by a slower component. 2. In the initial phase of clearance the half-life of neurophysin I was 1.50 min (s.e.m. = 0.03) and for neurophysin II was 1.74 min (s.e.m. = 0.05). In the slower phase of clearance the half-life of neurophysin I was 22.6 min (s.e.m. = 2.2) and for neurophysin II was 27.3 min (s.e.m. = 5.8). 3. The first component had a volume of distribution similar to the blood volume and the second component had a volume of distribution similar to the volume of extracellular fuid of the rat. 4. The metabolic clearance rates per 200 g of body weight were 1.94 ml/min (s.e.m. = 0.12) for neurophysin I and 1.29 ml/min (s.e.m. = 0.15) for neurophysin II. 5. Using whole-body autoradiography, the kidney was shown to be the major site of uptake of radioactivity in both virgin female and lactating mice.


Ketoacids in the treatment of uremia.

Ketoacids in the treatment of uremia. Essential amino acid supplementation (EAA) was compared with supplementation by a mixture (KA) of keto-analogues of valine, leucine, isoleucine, methionine and phenylalanine, plus the four remaining essential amino acids in stable chronic uremics. When KA were given after EAA, urea appearance fell and N balance improved (9 studies). When EAA were given after KA (5 studies), urea appearance and N balance did not worsen significantly during the 4-9 days of observation. Seven patients, including one on chronic dialysis prior to therapy, were given KA for 3-9 months as outpatients. In three, renal function clearly improved. Five became asymptomatic for intervals of 3-8 months.


Treatment of chronic uremic patients with protein-poor diet and oral supply of essential amino acids. I. Nitrogen balance studies. Twenty-six nitrogen balance studies were performed in 15 patients with severe uremia (Ccr mean value 5.1, range 2.3-8.5 ml/min) treated with an unselected protein-poor (16-20 g protein/day corresponding to 2.6-3.2 g N/day) diet and oral supply of the essential amino acids including histidine (2.6 g N/day). The general condition improved and the concentration of serum urea nitrogen decreased. The nitrogen balance, corrected for changes in total urea pool, was negative on the diet alone,-1.46 plus or minus 1.15 g N/day (mean plus or minus SD), but was positive when the essential amino acids were supplied, plus 0.84 plus or minus 0.68 g N/day. In four patients studied after 3 to 26 months of diet and amino acid therapy, during which time a further deterioriation of the renal function had occurred, the nitrogen balance was around zero in three and negative in one patient (-1.2 g N/day). The results show that it is possible with our new regimen to attain positive nitrogen balance or nitrogen equilibrium in severely uremic patients without excessive accumulation of urea in the body fluids.


Treatment of chronic uremic patients with protein-poor diet and oral supply of essential amino acids. II. Clinical results of long-term treatment. Twenty-six uremic patients - serum urea nitrogen (SUN) 110 MG/100 ml plus or minus 22.8 (mean plus or minus SD), serum cretinine (S-Creat) 13.2 mg/100 ml plus or minus 2.27, ratio SUN/S-Creat 8.6 plus or minus 2.26, and endogenous creatinine clearance (Ccr) 3.86 plus or minus 1.41 ml/min - were treated for three months or longer with an unselected protein-poor (16-20 g protein/day) diet with oral supply of the essential amino acids including histidine in high doses as coated tablets. The amino acids were instituted after an initial diet only period (mean 0.4 months). The average treatment time was 8.4 months (range 2.7-33.6). An improvement of the general condition was obtained, persisting for several months. SUN and SUN/S-Creat decreased on the diet alone, continued to decrease after one month, and increased slightly again after three months of treatment, but did not reach the initial levels for several months in spite of an almost doubled nitrogen intake. S-Creat increased after six months indicating a further deterioration of the renal function. In patients with initially low serum total protein (smaller than 6.5 g/100 ml, 9 patients), albumin (smaller than 3.5 g/100 ml, 10 patients), and total iron-binding capacity (smaller than 260 mug/100 ml, 11 patients) the values increased after one month on amino acids and were thereafter stable. No signs of bleeding tendency, progressive muscle atrophy, or progressive peripheral neuropathy were observed. - Five patients died due to cardiovascular maladies. A further 13 patients were withdrawn for medical reasons (overhydration, 4 patients; hypertension, 1 patient; nausea and vomiting, 7 patients; and pericarditis, 1 patient). - The renal function improved in one patient. Four patients received home dialysis training, three a kidney transplant. - The results indicate that it is possible to keep severely uremic patients free from uremic symptoms, counteract protein depletion, and even improve the nutritional status during long-term treatment with an unselected protein-poor diet supplementd with essential amino acids.


Recognizing the precursors of failure in school. Most of the children who fail in school come from educationally high-risk groups which are identifiable in the preschool years. Early recognition allows for constructive planning and in some cases the interposition of specific therapy (Table 1). Aall physicians should be aware of the relationships between these high-rish categories and future educational failure. The physician needs to accept responsibility for properly ensuring that the child will experience a wholesome, enriching experience in the school years. If the above measures were applied widely, a substantial reduction in the incidence of school failure among American children would be realized.


Reduction of enzyme efflux from skeletal muscle by diethylstilbestrol. We have previously shown that oral diethylstilbestrol (DES) lowers the high serum enzyme levels characteristic of Duchenne's muscular dystrophy (DMD). The present studies were undertaken to assess the effect of DES on the efflux of enzymes from isolated mouse skeletal muscle. Thirty-four male mice were used. Half received daily subcutaneous injections of 10 mug diethylstilbestrol-diphosphate (DES-DP) in saline for up to 3 wk and half daily saline injections. Left gastrocnemii were isolated from control and treated mice, and placed in separate incubation media at 37 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) from each was compared over a 4- to 5-hr period. In 15 of 18 there was a reduction in efflux of both enzymes from muscles isolated from DES-DP-treated mice. The greatest effect was noted during the second hour, when the mean efflux of each enzyme was reduced about 30%. Minor differences in muscle weight, water content, and enzyme activities did not explain the reduced efflux. These results suggest that DES has either reduced the permeability of the sarcolemma or enhanced the intracytoplasmic stability of these enzymes. This is the first drug reported to reduce the spontaneous enzyme efflux from isolated skeletal muscle. It remains to be established that a similar effect accounts for the reduction in serum enzyme levels when DES is administered to persons with DMD.


Electrophysiologic effects of glucagon on human cardiac muscle. The effects of glucagon (5, 10, and 40 mug/ml) on the amplitude and dueation of action potential, effective refractory period, dv/dt of phase 0 of action potential, membrane responsiveness, and contraction in human papillary muscles obtained from patients undergoing corrective open heart surgery were investigated. Glucagon, in none of the concentrations, produced any significant change in the amplitude and dueation of action potential, or in force of contraction. Shortening of the effective refractory period was not significant. Glucagon enhanced the conduction and the membrane responsiveness by increasing the dv/dt of phase 0 of action potential and a shift of curve to the left. It is suggested that the latter properties of glucagon would abolish the "re-entrant" type of cardiac arrhythmias produced by cardiac glycosides or other drugs that initiate and perpetuate arrhythmias dur to altered conduction.


Alpha and beta adrenergic-induced renin release in man. Changes in hemodynamic variables and renin release, induced with both alpha and beta adrenergic agonists, were studied in 5 normal men. Saline (0.9% NaCl), methoxamine (1.6 and 5.9 mug/kg/min), and isoproterenol (0.015 and 0.026 mug/kg/min) were infused individually in a random order for 30 min. Methoxamine and isoproterenol caused the predicted directionally opposite cardiovascular changes but caused nearly equal and dose-related increases in plasma renin activity, as measured by radioimmunoassay. Saline infusion had no effect. Propranolol (0.125 mg/kg) caused decreases in systolic pressure and heart rate, and a significant decrease in plasma renin activity. Propranolol prevented the renin-releasing effects of isoproterenol and methoxamine, but only the cardiovascular effects of isoproterenol. It appears that alpha or beta agonists stimulate renin release equally in man and that at least one step in renin is propranolol-sensitive. Such sensitivity may be independent of its beta receptor blocking activity.


A method for achieving blood pressure control expeditiously with oral minoxidil. Twelve patients with essential hypertension were treated aggressively with oral minoxidil in order to achieve blood pressure control as expeditiously as possible. Pretreatment blood pressure ranged from 159/109 to 238/161 mm Hg. Following an initial dose of 5 mg, subsequent dosage increments were administered every 6 hr until a fall in blood pressure was observed. The size of additional doses was determined by the magnitude of, and response to, the lowest effective dose and the therapeutic objective. Over a time interval of 24 to 42 hr, the blood pressure was reduced to normal or near normal in each case. Untoward hypotension was uniformly avoided. Analysis of the relationship between blood pressure response and cumulative dose indicates that at suboptimal blood pressure responses, it is safe and efficacious to give half the antecedent cumulative dose as a single dose in arriving at the therapeutic objective. The use of such a regimen should be considered as an alternative to parenteral drug administration in severe hypertension when immediate control of blood pressure is not required.


Prediction of drug dosage in patients with renal failure using data derived from normal subjects. A one-compartment model designed to predict alterations in persistence of drugs in uremic patients was constructed using information obtained from normal subjects. Data obtained from the literature in which the fraction of absorbed drug eliminated unchanged in the urine and the apparent elimination rate constants were compared in both normal control subjects and in severely uremic patients. Twenty-two drugs were examined. Despite changes in apparent volume of distribution and metabolism reported in uremia, the model was able to predict overall elimination rate constants in severe uremia with an error under 10% for 12 and under 20% for 7 additional drugs. The method appears to be most informative for drugs that tend to be retained in the presence of renal failure. Great error was observed with doxycycline and erythromycin. Studies with erythromycin lactobionate and a cupplate assay reduced the error for this drug from 56% for the glucoheptonate to 18%. Doxycycline is known to have a complex enterohepatic circulation. The model is offered as a useful approach to predict dosage adjustment in uremic patients with drugs for which data are not available.


Decreased plasma protein binding of diazoxide in uremia. The effect of uremia on the binding of diazoxide to plasma proteins was studied. An equilibrium dialysis technique, using diazoxide-minus14C at approximately 30 and 300 mug/ml in the plasma phase, was used to measure diazoxide binding to plasma. Serum albumin concentration (Alb) and serum creatinine (Cr) or blood urea nitrogen (BUN) were negatively correlated. By single regression analysis, per cent free diazoxide (%FD) correlated negatively with Alb and positively with Cr or BUN. When %FD was regressed simultaneously against Alb and Cr or BUN, Alb emerged as the sole determinant of %FD (p less than 0.001), indicating that creatinine or BUN correlated with %FD by their inverse correlation to Alb rather than by an effect on drug protein binding. At the levels of Alb studied, %FD varied over a 2-fold range. In a retrospective study of the influence of uremia on diazoxide effect in hypertensive patients, a relatively low correlation (r, 0.59) was found between BUN and hypotensive effect. Prospective studies involving correlations of drug effect with renal function and %FD are required to assess the clinical importance of decreased binding of diazoxide to uremic plasma.


Pharmacokinetics and metabolism of lidocaine in patients with renal failure. The kinetics of distribution and elimination of lidocaine and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were studied in 4 uremic patients on chronic hemodialysis. Each patient received a loading dose of 75 mg of lidocaine, followed by a 30 mug/kh/min lidocaine infusion. No toxic side effects from lidocaine were seen during the study. Average values for lidocaine steady-state plasma levels (2.3 mug/ml) clearance (12.3 ml/min/kg), terminal half-life (148 min), and total volume of distribution (1.9 L/kg) were found, and are similar to those values reported for normal subjects MFGX and after lidocaine infusion averaged 1/5-2/3 of the corresponding lidocaine level, as in nonuremic subjects, and plateaued by 6-8 hr. GX levels did not reach plateau by 12 hr and remained relatively unchanged after infusion. It is concluded that lidocaine infusion in uremic patients is safe, with no abnormal cumulation of lidocaine or MEGX. GX levels, however, may increase progressively, even after 12 hr.


Hemodialysis of phenytoin in a uremic patient. Removal of phenytoin by hemodialysis was determined in a uremic patient. The rate of appearance of the drug in dialysate, the plasma concentration with time, and the plasma clearance by dialysis were measured. Plasma protein binding of phenytoin was also determined. In spite of greatly reduced plasma protein binding in the uremic patient, removal rate was observed to be less than 10% of the rate of presentation of the dialyzer. During the 6-hr period of dialysis, the plasma concentration showed little change. The amount collected in the dialyase, 43.6 mg, was only a small fraction of drug in the body. These results indicate that replacement of phenytoin based on the amount of drug removed by dialysis is unnecessary in chronically dialyzed uremic patients. In addition, the utility of hemodialysis in phenytoin overdose is questioned.


Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites. Approximately 10% to 20% of isoniazid recipients manifest biochemical evidence of liver injury. A smaller number of patients develop clinically overt hepatitis. Isoniazid is metabolized in man at extremely variable rates, and the rate is under genetic control. Two separate clinical studies have noted a possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug. For this reason, 21 patients who had recovered from probable isoniazid hepatitis and 5 patients who previously had manifested biochemical evidence of mild isoniazid liver injury were genetically phenotyped as rapid or slow isoniazid acetylators by the sulfamethazine method. The rapid phenotype was found in 86% of patients with probable hepatitis and in 60% of the possible ones, whereas the expected frequency was 45%. Eximination of isoniazid metabolites revealed that rapid acetylators hydrolze much more isoniazid to isonic otinic hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazed is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. We suggest that release of the hepatotoxic hydrazino moiety of isoniazid in man is responsible for isoniazid liver injury.


Digoxin pharmacokinetics: role of renal failure in dosage regimen design. Radioimmunoassayed serum concentration and urinary excretion data for digoxin from azotemic patients were characterized using a 2-compartment open model. Urinary excretion rates of digoxin as well as serum concentration data are needed to accurately characterize the disposition of the drug. Seven patients with renal failure showed highly variable steady-state volumes of distribution (V-ss-D equals 195 to 489 liters/1.73 m-minus2) and t1/2beta values (1.5 to 5.2 days). This variability is a major limiting factor in the use of dosage regimen nomograms that assume a constant V-ss-D and a rigorous relationship between t1/2beta and creatinine clearance (Cl-CR). Body clearance (Cl-B) is a parameter that is affected by both elimination and distribution of drugs. A linear relationship between Cl-B and renal clearance of digoxin or Cl-CR was found and was used to develop a model-independent approach to calculation of maintenance doses of digoxin. Several methods for calculating steady-state serum concentrations of digoxin (C-ss-p) were compared with actual measurements obtained in 16 chronically medicated patients. Optimum computation of C-ss-p is obtained by use of digoxin renal and body clearances. Variability in the digoxin:creatinine renal clearance ratio is the major limiting factor in prediction of digoxin dosage regimens.


Commentary.  Major drug-prescribing patterns in general hospitals. Prescriptions of major drug classes were surveyed for one year in five teaching and five nonteaching general hospitals. Their overall rates varied over a two- to three-fold range in medicine, surgery, and pediatrics, but were uniform throughout the hospitals. Parenteral fluids and antibiotics represented over one half of the pharmacotherapy used in every specialty except medicine, where tranquilizers were the most frequently prescribed drugs. Prescribing patterns lacked consistency in obstetrics and newborn services, and generally with steroids, vasopressors, and anticoagulants. Significant variations also involved the use of fluids in pediatrics, diuretics in surgery, and vasodilators in medicine. These variations were too unpredictable and large to be attributed to specific differences among patient populations. Only two discrepancies were noted between teaching and nonteaching hospitals: tranquilizers were prescribed more often in the former, and vasopressors in the latter.


Methadone in man: pharmacokinetic and excretion studies in acute and chronic treatment. The biologic disposition of methadone in acute and during chronic administration was studied in 12 human volunteers. In the acute study a biexponential methadone plasma level decay was observed. The acute primary half-life (t1/2) of 14.3 hr in combination with the acute secondary t1/2 of 54.8 hr were longer than the single exponential chronic t1/2 of 22.2 hr determined in the same subjects. The urinary and fecal excretion of methadone and its mono-N-demethylated metabolite increased from 22.2% in the acute to 62.0% in the chronic phase of the study. The urinary metabolite 1 to methadone ratio tripled from the acute to the chronic phase. The pupillary effects of methadone monitored throughout 24 hr were nearly the same in magnitude in the acute and the chronic studies, whereas the plasma levels increased 3- to 8-fold following chronic methadone administration. These findings suggest that both dispositional and pharmacologic tolerance are involved in the development of tolerance following chronic administration of methadone.


5-fluorouracil with cytosine arabinoside in metastatic gastrointestinal cancer. A 2-drug combination chemotherapy regimen of 5-fluorouracil (FU) and cytosine arabinoside (ara-C) was used in 23 patients with gastrointestinal cancer. The drugs were administered as a mixture by daily continuous infusion for 5 days at 4-wk intervals. Dosages for each drug were: FU, 1.1 gm/m2/day and ara-C, 50 mg/m2/day. The incidence of leukopenia (WBC, less than 3,500/mm3) was 36% and of thrombocytopenia (platelets, less than 125,000/mm3), 18% during 33 courses administered at full doses. No clinical antitumor effects were observed in 18 patients evaluable for therapeutic response. The addition of ara-C to a nonmyelosuppressive dose schedule of FU results in potentiated marrow suppression, and the antitumor effect for the combination is less than would have been predicted for either drug alone.


The management of dental arch deformity in cleft lip and palate. Dental arch deformities develop in the embryo and fetus and are severe at birth. The clinician's responsibility to the patient is to guide the natural mechanisms of growth and compensation so that many aspects of the deformities will be alleviated. Scar tissue is an undesirable sequela to surgery, and should ideally not be adjacent to actively growing areas of the maxilla. There are three methods of managing arch deformities: by prevention, by interception, and by correction. The plastic surgeon modifies the deformity and thereby establishes the framework within which the orthodontist and prosthodontist may accomplish fairly minor alterations.


Mammary asymmetry.

Mammary asymmetry. Significant mammary asymmetry is not uncommon although accurate statistics are not available.  Modern techniques of mammary augmentation and breast reduction have resulted in effective methods of treatment of most such deformities.  The management of this problem was discussed.


The value of laparotomy and splenectomy in the management of early Hodgkin's disease. A report from the British National Lymphoma Investigation. Three hundred and nine cases of Hodgkin's disease have been investigated by laparotomy, splenectomy and biopsy of liver and abdominal lymph nodes. The findings are recorded and the value of and indications for the procedure discussed. Intra-abdominal involvement has been found in 86 out of 184 cases (47 percent) where other diagnostic methods, including lymphography, had not revealed disease below the diaphragm. as no clinical or histological parameter appeared reliably to indicate the likehood of intra-abdominal disease,  it is suggested that logically either laparotomy should be carried out in all Stage I and II cases, or that treatment policy should be governed by the high probability of intra-abdominal disease.


CCNU in brain tumours.

CCNU in brain tumours. CCNU, a nitrosourea compound, has been found effective in the management of both primary and secondary tumours of the brain. It is proposed to carry out an investigation comparing radiotherapy alone with radiotherapy and CCNU combined, in cerebral gliomata.


Review of strontium 87m scintigraphy in the detection of skeletal metastases from mammary cancer. Strontium 87m bone scanning was used in the assessment of 162 patients with breast cancer. Seventy-two patients had abnormal bone scans and in 63 (87 percent) these findings were subsequently confirmed. More metastases were detected by scanning and radiology than by radiology alone. There was a false positive rate of 7 percent. Of the 90 negative scans 23 showed evidence of metastasis either radiologically or at autopsy. This represented a false negative rate of 26 percent. The reasons for the false results are discussed particularly in relation to the problems of imaging the dorsal spine.


Intralobar septal oedema: 'D' lines.

Intralobar septal oedema: 'D' lines. A combined radiological and autopsy study of pulmonary oedema enables recognition of oedema lines other than Kerley 'A', 'B' and C lines. These have been designated 'D' lines. At least three varieties have been noted: (i) thick, long often angular lines seen mainly anteriorly overlying the heart shadow on the lateral film. These may also appear as horizontal or vertical band shadows, on the frontal view. (ii) Short and straight lines, occurring basally and often slightly thicker at the pleural surface, which on autopsy lung radiographs are associated with puckering of the pleura. They have also been recognised on lateral films where they resemble the pleural end of a fissure but have been seen in positions where fissures do not mormally occur, or in addition to the normal fissure. (iii) A subpleural reticular pattern surrounding spaces 1-2 cm in diameter. This has been noted only on autopsy-inflated lungs and not detected on in vivo chest radiographs. The long 'D' lines or D(i) lines occur in areas where 'B' lines are inconspicuous or absent and vice versa. Whereas 'B' lines are most prominent in areas of macroscopic alveolar pulmonary oedema, D(i) lines occur where macroscopic alveolar pulmonary oedema is often inconspicuous. The recognition that lines other than 'A', B and 'C' occur in case of pulmonary oedema greatly assists in the interpretation and diagnosis of the shadows on chest radiographs associated with pulmonary oedema.


Chyluria.

Chyluria. Thirty cases of chyluria seen in Rangoon during the years 1968-1973 have been investigated. Blood micro-filaria was positive in only a small number of cases. Renal function was not disturbed and blood eosinophil count was normal. The duration of symptoms varied from 3 months to 10 years. Males and females were equally affected and the disease was much more commonly seen in the 20 and 40 age group. Retrograde pyelography demonstrated pyelolymphatic reflux. Lymphangiograms showed numerous lymphatics  in the region of the calves and contrast was often seen in the calyceal system. The thoracic duct was patent in all the cases. Renal lymphatics were opacified in three patients who were investigated by intravenous urography. Para-renal cysts, pressure on the renal pelvis by an enlarged lymph node and dilated lymphatic vessels were associated features.


The spine as a point of reference for duodenal displacement by an enlarged liver in the sagittal projection. Normally, in the sagittal projection, the descending duodenum is situated to the right of the spine. There is a great range of variation in its position, so that a slight medial displacement by an enlarged liver or a mass adjacent to the latter cannot be diagnosed unless either an extrinsic pressure effect is demonstrated or a previous study is available for comparison. On a single study, displacement of the duodenum by an enlarged liver is suspected whenever the descending duodenum overlies the spine. This position is more indicative of displacement in sthenic than in asthenic individuals.


Estimation of renal size from radiographs: is the effort worthwhile? The weight of renal substance was measured in normal kidneys obtained at necropsy after removal of fat from the renal sinuses. This fat fo-med an average of 5 percent of the total renal weight, increasing only slightly with age. The weight of renal substance was correlated with measurements of length, width, depth and area obtained from radiographs. The best estimate of renal weight was made by using length alone. The effect of rotation of the kidney on its radiographic dimensions was also assessed. At the angles at which kidneys lie in the body, the longitudinal dimensions are less affected by small changes in rotation than the transverse dimensions. However, rotation within the range of arc normally found in the body may cause apparent diminution length of 1 cm or more.


The pre-operative diagnosis of renal hamartoma. The characteristic angiographic findings in renal hamartoma consist of: a large dilated feeding vessel passing through the mass, multiple multisacculated aneurvsmal dilatations (bunch of grapes), a delicate discrete discrete neovascularity without A-V shunting, and 'onion peeling' on the venous phase. In addition radiolucent areas within the renal mass indicate a high fat content. When these findings are present renal hamartoma can be diagnosed confidently. Racial nephrectomy and needless sacrifice of a whole kidney for a benign lesion can be avoided. Heminephrectomy may be sufficient, thus saving the patient valuable renal tissue. Four cases of renal hamartoma are presented. Plain film and angiographic studies are shown. All four showed the characteristic angiographic findings of renal hamartoma and were diagnosed pre-operatively.


Intracranial aneurysms presenting as mass lesions. Giant aneurysms within the carotico-basilar system usually differ in their symptomatology from the more common forms of intracranial aneurysms. By virtue of their size they may act as space occupying lesions and compress neighbouring structures. Diagnosis of these aneurysms as well as determination of position and size cnanot be carried out by clinical examination alone. Radiology with its special procedures is essential in confirming this diagnosis.


The radiology of arachnoid pouches.

The radiology of arachnoid pouches. The radiographic appearances in 14 cases with arachnoid pouches are reviewed. Their clinical summaries, operative findings and anatomical distribution are tabulated.


Radiological changes in serial x-rays of the foot and tarsus in leprosy. Most bone abnormalieis seen in serial films of the feet in leprosy were static being the end result of old disease. Changes over a period of time were observed in serial fims of 214 feet and these changes were due to a combination of infection, neuropathic changes and avascular necrosis occurring in anaesthetic feet. The bone abnormalities seen were absorption of toes and metatarsals; bone destruction; a neuropathic arthropathy of toes and metatarsals and various patterns of tarsal disintegration.


Educational videotapes-by and for the teaching department. To date television has not been used very much in teaching diagnostic radiology. The authors describe their method of producing educational videotape recordings suitable for teaching purposes. The adults point out that the procedure is relatively cheap in a department that possesses a videotape recorder and emphasise its value for specialised radiological teaching.


Micromethods for the simultaneous measurement of intracellular potassium and corticosterone output of isolated adrenal cortical cells. 1. A technique is described for the measurement of potassium and water spaces in less than 1 mul of packed cells.  2. The total potassium content of cell pellets is measured in a perchloric and nitric acid extract by flame spectrophotometry.  The potassium in trapped medium is estimated from the distribution space of hydroxy[-14C]methylinulin and subtracted from the total potassium content to give intracellular potassium content.  Corticosterone output was measured by radioimmunoassay.  3. The simultaneous measurement of total water from the [-3H]water space allows calculation of the intracellular water space.  4. Values obtained for intracellular potassium content, intracellular water space and calculated intracellular potassium concentration are presented for different preparations of isolated adrenal cortical cells.


Glucose metabolites in blood and adipose tissue of obese diabetic and non-diabetic subjects. 1. Glucose 6-phosphate, fructose 6-phosphate, fructose diphosphate, glycerol phosphate and uridine diphosphate glucose have been measured in human adipose tissue and blood from obese subjects under fed and fasting conditions and in obese diabetic and non-diabetic subjects before and after an oral glucose load (100 g).  2. Adipose tissue metabolites expressed as nmol/g wet weight correlated inversely with adipocyte diameter.  3. After fasting, fructose diphosphate and glycerol phosphate in adipose tissue decreased significantly.  4. The basal concentrations of metabolites in blood and adipose tissue were maintained at similar concentrations in diabetic and non-diabetic subjects despite very different blood glucose concentrations.  5. The significant increase in adipose tissue glucose 6-phosphate after the glucose load seen in the non-diabetic but not in the diabetic subjects suggest that glucose uptake is decreased in the diabetic adipocyte.


Effect of ethanol on the ventilatory responses to oxygen and carbon dioxide in man. 1. Hypoxic and hypercapnic ventilatory drives were measured in eight healthy male subjects before and after ingestion of ethanol, in a dose of 17 mmol/kg body weight.  2. A significant decrease in hypoxic ventilatory drive was observed at 20 min after ethanol (P less than 0.05).  A significant depression in hypercapnic drive was observed at 70 min after indigestion of ethanol (P less than 0.05).  The mean peak blood ethanol (24mmol/1) occurred at 20 min, at which time the lowest mean hypoxic drive was recorded.  3. Ethanol in moderate doses produced a depression of both hypoxic and hypercapnic ventilatory drives in normal subjects.  This suggests that ethanol may play a role in the precipitation of acute respiratory failure in certain patients in whom the ventilatory drive is already impaired, as in chronic airways obstruction.


Adrenergic responses to sustained handgrip in patients with juvenile-onset-type diabetes mellitus. 1. The response of plasma noradrenaline, arterial blood pressure and heart rate to sustained handgrip at 30% of maximal voluntary contraction was studied in patients with long-term juvenile-onset-type diabetes millitus and healthy subjects of comparable age. 2. There was no significant difference between the intensity and duration of handgrip in diabetic patients and healthy subjects. 3. Sustained handgrip produced an increase in plasma concentration of noradrenaline both in diabetic and healthy subjects but the response in the diabetic subjects was significantly less. 4. The increase in systolic blood pressure during handgrip was significantly greater in diabetic subjects than in normal subjects. The increases in diastolic and mean blood pressure did not differ significantky. 5. The increase in heart rate during handgrip was greater in healthy subjects than in diabetic subjects. The response was smaller in diabetic patients with retinopathy than in the patients without retinopathy. 6. The sustained handgrip test may be useful for the diagnosis of abnormal sympathetic nervous system and haemodnynamic responsiveness in diabetic patients.


The rate of isometric inspiratory pressure development as a measure of responsiveness to carbon dioxide in man. 1. A technique has been developed for assessing CO2 responsiveness by measuring the maximum rate of isometric inspiratory pressure change at the mouth [(dP/dt)max.].  2. By use of a rebreathing technique, the (dP/dt)max. response to CO2 was shown to correlate well the ventilatory response in thirty-two normal subjects.  3. The addition of an external flow resistance sufficient to reduce the ventilatory response by a mean of 33.4% produced no significant mean change in the (dP/dt)max. response in thirty subjects.  4. In six patients recovering from bronchial asthma, reduction of airways obstruction led to a mean increase in the ventilatory response of 109% without any significant mean change in the (dP/dt)max. response.  5. An increase in lung volume did not reduce the (dP/dt)max. response in five normal subjects. 6. At very high lung volumes, six normal subjects were able to develop a higher (dP/dt)max. during voluntary inspiratory efforts than has been recorded during spontaneous breathing response to CO2. 7. It is believed that (dP/dt)max. represents the initial rate of development of force by the inspiratory muscles before this can be modified by mechanical loading, proprioceptive feedback mechanisms or conscious response and can therefore be used to study changes in the motor output of the respiratory centre in response to ventilatory stimuli independently of pulmonary mechanics.


Renal kallikrein content of spontaneously hypertensive rats. 1. The kallikrein content of kidneys from spontaneously hypertensive and normal rats at birth and at age 37 days was determined.  2. Kallikrein values were significantly lower in the hypertensive rats.  3. It is suggested that the lowered kallikrein may be related to the development of hypertension.


Inhibition of renin secretion in the isolated rat kidney by antidiuretic hormone. 1. The effect of antidiuretic hormone (ADH) on isoprenaline-stimulated renin secretion was examined in the isolated rat kidney perfused with modified Krebs-Ringer saline.  2. Intrarenal infusion OF ADH effectively prevented stimulation of renin secretion by isoprenaline whilst increasing renal perfusion pressure.  3. The exclusion of calcium ions from the perfusion medium abolished the vasoconstrictor effect of ADH and attenuated the inhibitory effect of ADH on isoprenaline-stimulated renin secretion.  However, significant suppression of renin secretion was still apparent compared with experiments where isoprenaline was infused alone.  4. These observations indicate that ADH inhibits renin secretion and that this is effected by a direct action on the kidney.  Although this may be partly mediated by the rise in renal perfusion pressure, an additional direct effect of ADH on the renin-producing cell, which is dependent on the availability of calcium ions, is proposed.


Potassium changes in megaloblastic anaemia. 1. Serial measurements of serum potasssium and total-body potassium were made on eighteen patients with megaloblastic anaemia before the start of therapy and during the period of recovery.  2. In those patients who presented with an initial packed cell volume of less than 25%, a mean decrease in serum potassium of 0.4 mmol/1 occurred on average with 2.5 days of the start of therapy.  This was followed by a significant increase in serum potassium during the period of recovery.  There was a significant increase in total-body potassium in these patients, but this could be explained by increases in erythrocyte mass, erythrocyte potassium concentration and lean body mass.


Chronic effects of chlorothiazide on reabsorption by the proximal tubule of the rat. 1. The renal response to a low-sodium diet alone and a low-sodium diet plus the daily oral administration of chlorothiazide was examined in rats. Sodium restriction resulted in a decrease in sodium excretion until day 4, after which it remained constant. The administration of chlorothiazide resulted in an initial natriuresis. By day 6, however, the natriuresis had abated and thereafter sodium excretion remained the same as that of the low sodium group. 2. After the animals were in balance on their respective regimens, clearance and micropuncture studies were performed. The glomerular filtration rate was lower in the chlorothiazide-treated rats than in control rats and/or in the low-sodium group. End proximal tubule TF/Pinulin ratios were higher in the diuretic-treated animals than in control rats. TF/Pinulin ratios in low-sodium animals were lower than in the diuretic-animals but higher than in control rats. 3. These studies demonstrate that the escape from the chronic effects of chlorothiazide is due to a decrease in the glomerular filtration rate and to an increase in fractional reabsorption in the proximal tubule, resulting in a reduction in delivery of filtrate to the cortical diluting segment where chlorothiazide exerts its major inhibitory effect.


Determination of platelet and fibrinogen half-life with [75Se]selenomethionine: studies in normal and in diabetic subjects. 1. Simultaneous platelet and fibrinogen survival studies were carried out on a group of seven normal persons and eleven diabetic patients. 2. Survival time was calculated: (a) by measuring the interval between 50% of the maximum radioactivity in the anabolic phase and 50% of the maximum radioactivity in the catabolic phase, and (b) by fitting an exponential function to the decay phase of the curve. 3. With the first method, the normal group had a mean plaetelet survival which did not differ significantly from that in the diabetic group. With the second method, however, the platelet half-life in the diabetic patients was significantly shorter than in the normal subjects. 4. Fibrinogen survival was significantly shorter in the diabetic group with either method. 5. It is concluded that there is an increased utilization of platelets and fibrinogen in diabetic subjects.


The actions of bradykinin and eledoisin in the canine isolated kidney: relationships to prostaglandins. 1. The effects of two vasodilator polypeptides, bradykinin and eledoisin, were studied in isolated blood-perfused canine kidneys before and after administration of indomethacin, an inhibitor of prostaglandin synthesis, Bradykinin, but not eledoisin, releases renal prostaglandins. 2. Before administration of indomethacin, bradykinin decreased urinary osmolality and increased free qater clearance, whereas eledoisin did not affect the excretion of solute-free water. After administration of indomethacin, the renal vasodilator action of bradykinin was reduced but the vasodilator action of eledoisin was unaffected. 3. Fractional excretion of sodium was not affected by bradykinin before but was increased after administration of indomethacin. Reduction in glomerular filtration rate contributed to changes in sodium excretion produced by bradykinin and eledoisin. 4. The release of prostaglandins from the kidney by bradykinin amplifies the renal vasodilator action of the kinin and possibly mediates its effect on excretion of solute-free water.


Total body potassium in children, with particular reference to coeliac disease. 1. Total body potassium was measured, by wholebody counting, in children with coeliac disease and in children not having this disease, matched as closely as possible with respect to sex, height, weight and age. 2. The measured total body potassium in children with coeliac disease was not significantly different from that in the matched children. 3. The problems associated with such measurements, particularly those of interpretation, are considered.


Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity. 1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone  inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.


Effect of cellulose phosphate and dietary calcium restriction in primary hyperparathyroidism. 1. The bivalent cation-binding agent, cellulose phosphate, together with a low calcium diet was given for 6 days to nine patients with primary hyperparathyroidism subsequently verified at surgery. 2. Urinary calcium fell promptly by 8-4 mmol/24 h, and by 70% and reached amounts below 4-0 mmol/24 h in five of the nine patients. The magnitude of fall may have been related to increased synthesis of vitamin D by the skin in a sub-tropical environment. Plasma magnesium fell steadily and urinary magnesium fell by 80%. 3. The plasma calcium showed two types of response. In five patients there was no significant change because a reduction in calcium load was offset by a further increase in the already high tubular reabsorption of calcium. In the remaining four patients, the tubular reabsorption of calcium was at a higher level initially and failed to increase further on the experimental regime, with a corresponding fall in plasma calcium. 4. The hypercalcaemia of primary hyperparathyroidism can be explained by increased renal tubular reabsorption of calcium; net bone resorption makes only a small contribution but an additional factor dependent on the blood-bone equilibrium is not ruled out. 5. Comparison with other published data suggests that the fall in urinary calcium in response to a calcium-depleting regimen is prevented by concurrent depletion of inorganic phosphate and may be enhanced by concurrent depletion of magnesium. 6. Persistence of hypercalcaemia combined with an increase in tubular reabsorption of calcium in response to cellulose phosphate may be of diagnostic value in suspected primary hyperparathyroidism. 7. Cellulose phosphate may be of value in stone prevention in patients with primary hyperparathyroidism who are unsuitable for surgical treatment.


Liposomes as vehicles for the local release of drugs. 1. The rat testicle was used in studying the release of radio-labelled compounds from locally injected liposomes of various sizes, charge and lipid composition. 2. Large unsonicated liposomes markedly delayed the release of entrapped 125I-labelled albumin. Delay was due to liposomal entrapment rather than the presence of lipid per se and it was greater with neutral than charged liposomes. The albumin left the testis after release from, and not in association with, liposomal lipid. 3. Large unsonicated liposomes also delayed the release of entrapped actinomycin D and 5-fluourouracil. The former retained its cytotoxic activity and resulted in focal, dose-dependent tissue necrosis. 4. Small sonicated liposomes did not delay the release of entrapped 125I-labelled albumin, and enhanced release of actinomycin D, producing high concentration of these compounds, which were released in association with liposomal lipid, in draining lymph nodes.


Coma, hyperthermia, and bleeding associated with massive LSD overdose, a report of eight cases. Eight patients were seen within 15 min of intranasal self-administration of large amounts of pure D-lysergic acid diethylamide (LSD) tartrate powder. Emesis and collapse occurred along with sign of sympathetic overactivity, hyperthermia, coma, and respiratory arrest. Mild generalized bleeding occurred in several patients and evidence of platelet dysfunction was present in all. Serum and gastric concentrations of LSD tartrate ranged from 2.1 to 26 ng/ml and 1000 to 7000 mug/100 ml, respectively. With supportive care, all patients recovered. Massive LSD overdose in humans is life-threatening and produces striking and distinctive manifestations.


Cocaine identification.

Cocaine identification. Scott's three-solution procedure was examined and should be considered the method of choice for testing pure compounds suspected to be cocaine. Because of false positives for cocaine encountered with mixtures of drugs such as lidocaine and phencyclidine, Scott's procedure should be confirmed using Kodak's Field Kit for alkaloids, or a similar kit. As pointed out by Winek [3], all field testing procedures should be followed by laboratory confirmation.


Rapid mass screening and confirmation of urinary amphetamine and methamphetamine by gas chromatography. A rapid and simple procedure is described for the mass screening and confirmation of amphetamine and methamphetamine in urine using gas chromatography with flame ionization detector. The amphetamine drugs are screened as free drugs on a 10% Apiezon L-10% KOH column and confirmed as their trifluoroacetamide derivatives on a 3% OV-17 column. This dual approach eliminates false positives and interfering substances that may be present in the urine and is, therefore, specific for amphetamine and methamphetamine.


Rapid analysis of the central nervous system stimulants, amphetamines, via gas chromatography-mass spectrometry: rapid acylation in the presence of a mercury catalyst. A simple, direct, instantaneous, and quantitative acetylating procedure for amphetamines has been developed. The method uses trifluoroacetic anhydride in the presence of mercuric trifluoroacetate as a catalyst. The product was characterized by a gas chromatography-mass spectrometry system. The salient features of this technique are: (a) rapidity of analysis; (b) no previous cleanup to remove adulterants; and (c) detection of amphetamines at the picomole level. We have routinely applied this technique for court samples and law enforcement authorities. The method could prove to be applicable, with minimum amounts of involvement in sample preparation, to the analysis of a variety of compounds containing an acyl displaceable hydrogen.


Drugs of abuse radioimmunoassay directory. This clinical brief is a survey of procedures, components and kits presently available for detecting and quantitating drugs of abuse in biologic fluids by radioimmunoassay (RIA).


Mental health training and consultation with suburban police. A community mental health consultation and education program with 10 suburban police departments has helped foster the development of an awareness of mental health issues on the part of police officers and their chiefs and increased their orientation toward prevention of problems before they arise. The keys to success in this project have been flexibility in the application of consultation and training modalities, a willingness to view the world through the police officers' eyes, and the cooperative involvement of officers and their chiefs in all phases of program planning.


A psychotherapeutic approach with elementary school teachers. The tradional "lectures delivering" approach to classroom teachers used by mental health practitioners is investigated in the present study. An attempt is made to demonstrate the validity of preventative work in helping elementary school teachers as important agents in the promotion of more positive mental hygiene in the classroom and by adding to the lectures the variable of group therapy--"ego-sparing" techniques type. The latter approach seems to promote a teacher's own sense of security in dealing the pupils, an easier acceptance of differences in others, and, finally, it tends to stimulate the development of a teacher's own ability to deal sensibly, more conscientiously, and more realistically with daily problems.


The psychiatrist-administrator: odd man out? The development of community psychiatry as a recognized subspecialty of psychiatry and the concomitant growth of community mental health programs have once again brought into focus the role of the psychiatrist-administrator in the practice of public psychiatry. This paper explores the principal conflicts that the psychiatrist-administrator faces in his multiple roles as a physician, psychiatrist, administrator, community services planner, and clinician. Unless he can work toward a resolution of the conflicts and problems that arise, he is in danger of becoming the "odd man out"--the psychiatrist-adminstrator who does not have complete acceptance from any of the groups to which he belongs and within which he is trying to define his combined and complex role.


The nature, prevalence, and level of awarenes of "curanderismo" and some of its implications for community mental health. This study is exploratory research into the nature, prevalence, and level of awareness of curanderismo (Mexican folk psychiatry), and some of its ramifications for community mental health, as perceived by the staff of two community mental health centers serving largely Mexican-American populations on Chicago's south side. The sample interviewed consisted of virtually the entire staff--29 persons in all, 14 from one community mental health center and 15 from the other. Data collection was done individually with a 4-page, 31-question interview, made up of personal-data questions, multiple-choice questions, and open-ended ones.


Training the secretary in community mental health: a second model for integrating secretaries into the therapeutic team in community mental health. The secretaries in community mental health centers have functions that transcend their job descriptions. Their performance of these functions contributes to the success or failure of their centers' therapeutic programs. The Mental Health Training Institute of North Carolina initiated two separate pilot training programs within 1971-1972, aimed at heightening the secretaries' appreciation of their role within their centers and at facilitating their integration into the therapeutic team. This paper is a discussion of the second of these two programs.


Guidelines for the functioning of a helping service. The purpose and the operation of an effective helping service are defined along the principles developed by R. R. Carkhuff. A functional operationalism directly linking each aspect of a helping service to the objective of servicing the needs of those people for whom the service exists is developed. The personal fitness of the staff as defined by their effectiveness at living is identified as the critical variable determining service effectiveness. The level of staff performance on the operational indices of physical, emotional, and intellectual functioning including, specifically, the interpersonal dimensions of empathy, respect, genuineness, concreteness, confrontation, and immediacy is designated as the operational basis for the organizational decisions of hiring, firing, promotion, and role assignment. Systematic programs designed to meet specific client needs serve to complete staff and service effectiveness.


Drug and risk perception on ninth-grade students: sex differences and similarities. Sixty-two secondary school students were observed in their classrooms over 5 weeks of intensive drug information for within-group changes in their perceptions. "Peer pressure" and "kicks" were cited as reasons for starting and using drugs; but peer pressure had relatively greater strength for girls than for boys, and curiosity increased for girls. Boys and girls differed in reasons for stopping drugs (peer and professional help for girls, and punishment for boys). In rating the relative dangers and pleasures of marijuana and heroin, most students did not discriminate effectively between the two drugs, although ratings of marijuana dangers decreased. Unexpectedly, responses concerning the health hazards of heroin did not increase. In a situation simulating risk under peer pressure, boys chose targets as appropriate for their skill as did the girls.


Mental health ideologies of psychiatric nurses. Students in graduate programs of psychiatric nursing across the United States were surveyed in terms of their individual commitment to three major mental health ideologies--community mental health ideology, psychotherapetic ideology, and somatotherapeutic ideology. In contrast to earlier research, which had indicated that psychiatric nurses are ideologically neutral, it was found in the present study that as a group these 386 young psychiatric nurses were more committed to community mental health ideology than to the other two psychiatric orientations measured.


Multiple views of a school mental health project: a needed focus in community programs. A school-based community mental health program, emphasizing early detection and prevention of school maladaptation, was analyzed from the perspectives of participants with different roles and stakes. Program founders tended to value it more than those who carried out its "line" functions. Some differences are identified between what was valued theoretically about the program and how participants actually allocated their time. Differences in perspectives among program participants at various levels and differences between de jure and de facto aspects of program operation are viewed as sources of potential friction. Such difficulties tend to increase as initially simple program models are extended to diverse settings with different needs, problems, resources, and personnel.


Imroving mental health through community action. This article reviews briefly some of the theoretical ideas and empirical findings which support the notion that societal processes that produce stress may lead to psychiatric disorder. Based on this, a conceptual model for improving mental health through community action is outlined. A case report is then given describing one effort to apply the model in an urban mental health center. Characteristics of the model are thus clarified and illustrated. Next steps are then suggested whereby the effectiveness of this approach to mental health through community action can be further developed and evaluated.


Changes in general haemodynamics and renal function during exercise in patients with arterial hypertension. Basic haemodynamic parameters were measured in 58 men in various stages of essential hypertension, 18 patients with hypertensive form of chronic glomerulonephritis, and 23 practically healthy persons during graded exercise in the supine position on a bicycle ergometer for 30 minutes. During exercise, the systolic pressure rose in all persons investigated, whereas the diastolic pressure markedly increased only in patients with arterial hypertension. The cardiac index increased, according to the intensity of the exercise equally in the healthy persons and in patients in early stages of essential hypertension; a lesser increase in the cardiac index was observed in patients in late stages of hypertension and in those with chronic glomerulonephritis. The increase in the cardiac index during exercise is essentially due to an increase in the heart rate; the stroke index increases only slightly, and in later stages of essential hypertension even decreases. The total peripheral resistance diminishes during exercise, but less so in patients with arterial hypertension in whom it is distinctly higher than in healthy persons. The circulating blood volume decreases during exercise in consequence of a decrease in plasma volume, whereas the haematocrit value increases. Renal blood flow and glomerular filtration decrease during exercise, both in healthy untrained persons and in patients with arterial hypertension. In patients in late stages of essential hypertension and in those with glomerulonephritis, the above parameters decrease more markedly and at lower exercise intensity than in healthy persons.


Arterial-wall tissue factors influencing haemocoagulation, and their release into circulation in endarterectomy. The wall of lover-limb arteries affected with severe atherosclerosis contains a Complex of substances with pro- and anticoagulative activities. The arterial wall, traumatized in endarterectomy by separation of the individual coats, releases procoagulative substances into blood circulation. The most conspicuous local manifestations of hypercoagulation and hypofibrinolysis appear on the day of surgery. The artery operated upon releases the thromboplastic factor for nine days; substances shortening the thrombin time (antiheparin substance, thrombin accelerator), for five days; and inhibitors of fibrinolysis, for four days after operation. A correlation was found between the regenerative process in the endarterectomized artery and the dynamics of the release of tissue factors influencing the haemocoagulation.


Renal venous renin in patients with renovascular hypertension. Renal venous and peripheral plasma renin activities were determined in 29 operated patients with renovascular hypertension and in 10 patients with essential hypertension. The majority of patients with renovascular hypertension exhibited elevated peripheral plasma renin activity, but the most striking increase of renin activity was demonstrated in the venous effluent of the involved kidney. Using data obtained in patients with essential hypertension, the ratio of renal vein renin activity not exceeding 1.4 was assumed normal. In patients with renovascular hypertension, the values above 1.4 were accepted as lateralizing ratios. In 78.6 % of patients with unilateral renal artery stenosis and a lateralizing renal vein renin ratio, normotension or improvement of blood pressure control were obtained post-operatively. The discussion emphasis the importances of renal vein renin estimations with the calculation of renal vein ratio for determining the functional significance of renal artery stenosis and for predicting the surgical outcome


Evaluation of the asymmetry of renal sodium excretion in patients with renal artery stenosis. Despite the fact that excretion and reabsorption fractions of sodium and water should express complementary aspects of the same renal process, calculation of ratios of excretion and reabsorption fractions in both kidneys can lead to differences in results. A theoretical analysis demonstrates that from the physiological point of view it is more correct to evaluate asymmetry on the basis of the ratios of reabsorption fractions. In 13 patients with renal artery stenosis, changes in reabsorption and excretion fractions of sodium, all osmotically active substances and water investigated before and after furosemide administration. The ratios of reabsorption fractions of sodium increased in 9 cases and syymmetry in function on the two sides was accentuated. It is suggested that separate investigation of tubular reabsorption of sodium and water in patients with renal artery stenosis should be combined with administration of furosemide and that the evaluation should be carried out on the basis of calculation of reabsorption fractions.


The effect of some antithrombotic drugs on experimental arterial thrombosis. The model of arterial thrombosis in rats used in this study is especially suitable for testing the preventive effect of antithrombotic drugs. An oral anticoagulant was ineffective in this model. Heparin, streptokinase, acetylsalicylic acid and dipyridamole were only moderately effective whereas highest effectiveness was attained by combining heparin with acetylsalicylic acid.


Effect of vanadium on tissue respiration in organs and on cholesterol metabolism in guinea pigs with experimental atheroclerosis. In experiments on guinea pigs with experimental atherosclerosis, vanadium pentoxide retarded the development of vascular pathomorphological changes, supported cholesterol metabolism, and activated oxidoreductive processes. Correlation and regression analyses proved that vanadium pentoxide has a beneficial effect on the course of experimental atherosclerosis in guinea pigs to the influence of this drug on oxido-reductive processes.


Right-left discrimination skills of hemiplegic persons of limited intelligence. Past research has indicated a relationship between degree of unilateral usage of body parts and right-left discrimination skills. Further evidence for such an association was sought by comparing the scores of hemiplegic persons of limited intelligence on a test of rather advanced righ-left discrimination skills devised by the authors to those earned by a control group of non-hemiplegic persons matched on the variables of age, sex, race, and IQ. Mean scores of the hemiplegic group were significantly higher than those of the control group. Seventeen out of 21 hemiplegic persons scored higher than their matched controls. Results are discussed in terms of a possible causal relationship between perceived visual and kinesthetic differences between the right and left sides of one's own body and right-left discrimination in  external space. Lesser degrees of inter-hemispheric communication among hemiplegic persons also are mentioned as a possible causal factor.


Visual form perception in deficient and normal readers as a function of age and orthographic-linguistic familiarity. The present investigation directly assessed the hypothesis that poor readers sustain no basic disorder in visual-spatial functioning. In order to extend pervious results to younger children, the performance of poor and normal readers from both the second and sixth grades was compared. Adopting the format of an earlier investigation, a visual recall task was employed as the dependent variable, and it was predicted that poor readers would perform as well as normals with stimuli taken from Hebrew, an unfamiliar orthography. Accordingly, non-Hebrew poor and normal readers were compared with normal readers learning Hebrew on the production of varying length Hebrew words. As anticipated, children in the non Hebrew reader groups performed comparably on this task, but the performance of these subjects was inferior to that of children in the Hebrew groups. The data support the contention that visual perceptual disorder is an unlikely source of reading disability.


Recognition of upright and inverted faces presented in the left and right visual fields. Pictures of upright and inverted faces were unilaterally presented in either the left or right visual field. Subsequent recognition performance was found to be superior for faces falling in the left visual field regardless of orientation. The results are discussed in relation to Yin's (1970) ideas concerning a face-specific recognition system located in the right hemisphere.


The relation of visuospatial dysfunction to digit span performance in patients with cerebral lesions. DSF and DSB performance was compared in hospitalized controls and right and left brain lesion groups dichotomized for the presence or absence of visuospatial deficits. Digit Span performance was also correlated with WAIS Similarities and Block Design and Raven Coloured Progressive Matrices. No differences between groups were observed on DSF. On DSB patients with brain lesions had lower scores than controls and brain-lesioned patients with visuospatial deficits had lower scores than those without. DSB correlated significantly with WAIS Block Design and Raven Coloured Progressive Matrices supporting the hypothesis that visuospatial ability is needed to mediate proper DSB performance. The correlation of DSB with WAIS Similarities, however, lends support to the idea that low DSB may merely reflect severity of cognitive deficit.


Critical reading at the sentence level in aphasia. A sentence-reading test was devised in order to assess the aphasic's ability to detect errors in written discourse. One hundred pairs of sentences, each containing one correct and one erroneous sentence, were presented to the patients, who were required to locate the error in one of the two sentences. So that comprehension in the auditory and visual modalities might be compared, the identical test was administered orally to a subset of the aphasic population. Contrary to expectations, there was no difference in overall scores between patients with anterior and posterior pathology. Anterior patients performed somewhat better on the oral version, posterior patients on the written version of the test. Finally, an examination of errors revealed a regular order of difficulty in sentences which featured contradictions to "real-world" knowlege, irrespective of the locus of brain damage, while the order of difficulty of sentences featuring syntactic deviations differed appreciably, depending on the locus of lesion. An attempt is made to relate these findings to current experimental and clinical knowledge.


The problem of repetition: a study of "conduction" aphasia and the "isolation" syndrome. The classical view of conduction aphasia and the isolation syndrome holds that there is, respectively, preferential damage to, or sparing of, a (repetition) pathway between the posterior and anterior speech areas. This concept is deeply entrenched in neurological thinking, but is supported neither by clinical nor pathological evidence. These two disorders are explained from the standpoint of a more dynamic theory of language organization. This new approach has implications for our understanding of anatomical relationships "between" the speech areas.


Central (or conduction) aphasia in a Japanese patient. A case of relatively pure conduction aphasia in a 66 year old woman is reported. A detailed linguistic analysis was performed and the patient's handling of the phonogrammic and ideogrammic aspects of the Japanese language was analysed. The patient showed a comparable pattern of difficultly in the following four operations: (1) naming of pictures (2) reading aloud of Kanji and Kana characters, (3) repetition of words and (4) transcription of heard words into Kanji and Kana characters. Of special note was the patient's superior written transcription of the ideographic symbols and the superior oral reading of the phonogrammic symbols. These results indicate that the patient had a basic defect in expressing the predetermined target word in verbal or writter form. From the analysis of Kana writings it is hypothesized that the in ability to establish a stable and distinct acoustic word image is responsible for this basic expressive difficulty leading to both paraphasic and paragraphic errors.


Go - no go learning after frontal lobe lesions in humans. 48 patients with unilateral frontal or non-frontal cortical lesions were given a go - no go learning task. Patients with frontal lesions in either hemisphere took longer to learn the task and made more false "go" responses than control patients. They also, unlike controls, took longer to make in correct positive responses than correct positive ones. Medial frontal lesions were found to be particularly important in giving rise to poor performance on this task. It is suggested that this task is non-unitary in nature and that the medial area may be important for more than one ability.


Agnosic behavior in anomia: a case of pathological verbal dominance. The interrelation of perceptual and verbral process was explored in a fluent aphasic with a naming disorder. This patient performed extremely well on complex perceptual tasks as long as he was instructed to remain silent or to count aloud. Whe he began to talk about what he was doing, he misnamed many test items and behaved as if they were what he had called them. The verbal interference effect is explained in terms of cerebral dominance and interhemispheric interaction and it is suggested that a similar mechanism may apply in classical cases of agnosia.


Hand preference in sequential and spatial discrimination tasks. Hand preference in sensorimotor discrimination tasks was tested on 80 right handed subjects in four experiments. One set of experiments compared the abilities of the two hands to perform sequential tasks. The other set compared spatial abilities of the two hands. Within each set one experiment involved unimanual performance, and the other bimanual performance. The results showed that subjects performed better with their right hand on the bimanual sequential task, and better with their left hand on the bimanual spatial task. No hand preference was found in the unimanual tasks. The results are interpreted as reflecting the differential sensorimotor dominance of the left and right hemispheres for sequential and spatial tasks respectively.


Independent functioning of the two cerebral hemispheres for recognizing bilaterally presented tachistoscopic visual-half-field stimuli. Bilateral tachistoscopic presentation of verbal stimuli produces a significantly larger right visual half-field (VHF) superiority than does unilateral presentation, when fixation is controlled by a center digit. This experiment tested whether the increased asymmetry was due to (a) subjects attending the right VHF and ignoring the left VHF or (b) interference between the hemispheres due to competition for the left hemisphere language areas. Words, shaptes, and pictures of faces were presented bilaterally to each VHF, with fixation controlled by a center digit. In three conditions, the same type of stimuli was presented in each VHF (e.g., a word in both the left and right VHF). In two conditions words were presented to one VHF and nonverbal stimuli to the opposite VHF (words paired with words and words paired with faces). It was found that the stimulus pairings did not affect VHF asymmetry for any stimulus. Words showed a large right VHF superiority in all conditions. Shapes showed a significantly smaller right VHF superiority in all conditions. Faces showed no VHF asymmetry in any condition. It was concluded that attentional factors were not important since shapes or faces could be recognized accurately from the left VHF without lowering verbal recognition from the right VHF. Thus the low recognition accuracy from the left VHF is specific for verbal stimuli rather than attentional. The interference hypothesis was also not supported since all the right VHF stimuli (words, shapes, or faces) were associated with low recognition of words from the left VHF. It was suggested instead that VHF asymmetry under unilateral and bilateral presentation reflect two different mechanisms. Under conditions of unilateral presentation, VHF asymmetries are caused by loss of information when any given stimulus must cross the callosum to reach the hemisphere specialized for its processing. However, with bilateral VHF presentation and fixation control, the two hemispheres act as independent channels for information processing. Under this condition, each hemisphere recognized the stimulus from its contralateral VHF. Thus the large right VHF superiority for words with bilateral presentation reflects the superior ability of the left hemisphere for verbal recognition.


Superior recall of letters in the right visual field with bilateral presentation and partial report. The present investigation addresses itself to the question of whether a right visual field effect would emerge under conditions of bilateral letter presentation and partial report. Tachistoscopic trials consisting of eight letters, four in each field, were presented for 100 msec., to twenty right-handed adults. Ss were instructed to report the content of only one field on each trial. Under these conditions a right field superiority was obtained and an interaction between field and stimulus position. The field asymmetry appears to reflect the operations of cerebral dominance while the interaction suggests the influence of mnemonic factors.


Comprehending a word: the influence of speed and redundancy on auditory comprehension in aphasia. To assess the contribution of various factors to comprehension of a target word, an auditory comprehension test was devised and administered to a series of aphasic patients. Patients were required to select from an array that picture which corresponded to a spoken target word. Each patient heard the target word under five conditions: (1) target spoken alone; (2) target embedded in a neutral (low redundancy) sentence enunciated at a normal rate of speaking; (3) target in a neutral sentence enunciated at a slow rate of speaking; (4) target embedded in a sentence containing semantic support (high redundancy); (5) target embedded in a sentence containing a semantically-deceptive element. Semantic redundancy and rate of presentation made contributions to comprehensibility. Semantic confusions were prevalent among all aphasics but, contrary to earlier reports, posterior patients were especially prone to acoustic confusions. Except for conduction aphasics, patients were more likely to confuse words which began with the same sounds than words which ended with the same sounds. Patients with adequate comprehension at the start of the testing displayed a uniform tendency to improve on the conditions administered later, while those with impaired comprehension at the start usually did not.


Imagery as an aid to retrieval for Korsakoff patients. Six Korsakoff patients and six alcoholic controls learned a five item P-A task under each of the following three learning conditions; Rote, Imagery, and Cued learning. Under all conditions the Korsakoff patients took more trials to learn than did the control patients. However, both imagery learning and cued learning were easier than rote learning for the Korsakoff patients when recall was used as the learning index. When a recognition measure was used instead of the recall, imagery learning proved easiest with no difference existing between cued and rote learning. In a second experiment, the patients were given the cue (a mediating link) during presentation, but not during retrieval. Under this condition the Korsakoff patients learned no more rapidly than they did by rote regardless which response measure was required. It was concluded that imagery can aid both storage and retrieval of verbal information for Korsakoff patients, while cuing aids only the retrieval process.


Effects of phonological and tactual similarity on serial object recall by blind and sighted children. Two experiments tested 30 blind and 60 sighted children on serial recall of easily named objects, differing (1) in name sound and tactual characteristics; (2) in name sound, but similar in feel; and (3) in feel, but similar in name sound. Significant recall decrements were found for tactually similar relative to dissimilar series for both blind, and sighted subjects able to cope with set-sizes of up to 5 items, but not for subjects under a set-size of 6. Blind and sighted children tested under set-sizes of 4 and 5 or 6 items showed recall decrements for phonologically similar compared to dissimilar lists, but subjects under a set-size of 2 or 3 did not. It was argued that the results demonstrate both tactual and phonological encoding of tactually presented material by children.


Hemispheric lateralization for speech perception in stutterers. Sixteen adult, right-handed, moderate-to-severe atutterers (12 males, 4 females) and 20 nonstuttering controls (10 males, 10 females) were given a dichotic nonsense-syllable test to determine hemispheric lateralization for speech. Both male and female stutterers evidenced right-ear advantages in syllable identification similar in magnitude to those found for normals. These data confirm other reports of no difference in cerebral speech lateralization for stutterers and nonstutterers and, therefore, lend no support to theories that relate stuttering to abnormalities in cerebral lateralization. Acknowledgments. This study was conducted while the authors were at the University of Connecticut, Storrs. The assistance of Dr. R. L. Webster, the staff of the Institute for Behavioral Research, and the Departments of Psychology and Linguistics at the University of Connecticut is gratefully acknowledged.


Characteristics of visual stimuli and naming performance in aphasic adults. A confrontation naming task utilizing objects and pictures from the Porch Index of Communicative Ability was presented to 14 aphasic patients. Both initially correct and self-corrected naming responses were compared for the two sets of visual stimuli. In contrast to some studies that have also varied the physical characteristics of size, color and dimensionality, the present study (as well as two other studies) found no significant differences in naming performance for aphasic patients. This evidence would suggest that a choice between pictures and objects will seldom be crucial to diagnosis or therapy with aphasic naming problems.


Xipamid, a potent new diuretic.

Xipamid, a potent new diuretic. The effects of xipamid and frusemide were comapred in 9 oedematous patients. Xipamid was found to be equipotent with frusemide in doses of 40 mg. and 80 mg., with respect to its effect on sodium and water excretion. The time course of action of xipamid was observed to be more prolonged than that of frusemide. It is concluded that xipamid is a potent and safe diuretic.


A multi-centre trial of mazindol ('Teronac') in general practice in Ireland. In a multi-centre trial of mazindol ('Teronac'), a new anorectic agent unrelated to amphetamine, 274 male and female patients were treated by 53 investigators in Eire. All patients were overweight according to the Metropolitan Life Assurance Company Tables, and 166 patients completed the treatment regime of one 2 mg. tablet daily and a 100 calorie diet for 12 weeks. The average weight loss was 18.8 lbs. (8.5 kg.); 85% of patients reported good appetite supression and good ability to adhere to their diet, and the attending physicians rated mazindol as being of considerable help in 92% of the patients. Mazindol was well tolerated, only 29 patients dropped out of the trial because of side-effects.